Systems For Synchronizing Different Devices To A Cardiac Cycle And For Generating Pulse Waveforms From Synchronized ECG and PPG Systems

ABSTRACT

A system for synchronizing a target device to a cardiac cycle, including: (a) a target device that collects data or performs an operation that is to be timed to the cardiac cycle; (b) a signaling device that emits a signal indicating the occurrence of a cardiac contraction and/or ECG feature; and (c) a calibration device that determines the relationship of the signal from the signaling device to the actual cardiac cycle. In operation, the calibration device calculates a time offset between the timing of the cardiac contraction as determined by the signaling device and the timing of the cardiac contraction and/or ECG feature as determined by the calibration device, and then provides the time offset to the target device.

RELATED APPLICATIONS

The present application claims priority to U.S. Provisional PatentApplication 62/955,196, entitled “System For Synchronizing DifferentDevices To A Cardiac Cycle”, (filed Dec. 30, 2019), the entiredisclosure of which is incorporated herein by reference in its entirety.

TECHNICAL FIELD

The present invention relates in general to systems for synchronizingthe operation of various medical equipment and fitness devices to a useror patient cardiac cycle, and in particular to synchronizing ECG and PPGsystems to the cardiac cycle.

BACKGROUND OF THE INVENTION

A wide variety of medical equipment and fitness devices either gatherinformation or perform operations that are timed to the cardiac cycle ofa user or patient. For example, simple fitness tracker watches andwearable bands are common devices that are used to detect a user's heartrate. In addition, the grippable handles of exercise bicycles have alsobeen fitted with sensors that can determine the user's heart rate.

The majority of these fitness tracking devices monitor a single biologicparameter (e.g. heart rate from one ECG lead). With such monitoring,signal delays, even significant ones, do not change the fitness trackeroutput. Obtaining more insight into the underlying biologic status andhow it relates to optimal function requires coordinating input fromdifferent modalities in different locations on the body simultaneously.Coordinating input from multiple modalities at multiple locationsrequires a level of accuracy that a single device utilizing a singlemodality does not have. Signal delays that may be tolerable in thelatter situation may be problematic with multiple modalities and/orlocations on the body. This is especially true with inexpensive deviceswhere cost considerations may not have placed a premium on minimizingsignal processing delays.

All monitoring devices will have a delay between event detection andevent notification, due to the internal circuitry of these devices. Forexample, a fitness tracker may sense a heart contraction (and signalthat it has occurred) a few micro-seconds after the heart contractionhas actually occurred. If the only task the monitor does is measure theheart rate, that rate will not be changed by a processing delay, so longas this delay applies to all beats. Since this signal delay tends to bethe same length of time after each detected heartbeat, the heart ratecan be accurately determined—but only because the same signal delayoccurs every time after a heart beat has been detected.

Even very small timing delays can cause problems in scenarios thatattempt to use multiple sensors at multiple sites when attempting to domore than simply determine the user's heart rate. For example, thesedelays cause problems when attempting to determine a user's Pulse WaveTransit Time (PWTT) or Pulse Wave Velocity (PWV). The PWTT is ameasurement of the time between the onset of the heart contraction andthe time at which the flow of blood reaches a given location on thepatient's body (typically measured on a patient's fingers or toes).Currently, obtaining a PWTT measurement requires an expensive and/orbulky ECG system detecting the QRS signal and a coordinated PPG(photoplethysmography) device at a patient's fingertip measuring thechange in absorption of light projected at the tissue.

If the ECG signaling system detecting cardiac activity operatesindependently of the target PPG device, and has a delay between cardiacevents and signaling of such events that the device collecting the PPGdevice is not aware of or cannot calibrate, then one cannot accuratelycalculate the PWTT. There is the additional problem that the signalingECG device internal clock and target PPG device internal clock—if notactively synchronized—will diverge over time, even though this may be avery slight divergence over the biologic times involved. Nevertheless,some sort of synchronization or hierarchy of timing is required to makeuse of the combination of the ECG and PPG signals. Synchronization canbe achieved by using a 3rd device with a known, accurate, and calibratedcollection of sentinel signal (e.g. the ECG QRS complex). This device,which can collect data from the signaling device and compare the timecollection against its own clock and data collection, can then assessthe delay inherent in the original signaling device. This calibrationdevice can then transmit this delay information to the target device sothat the target device, which is also receiving the signal from thesignaling device, can accurately time the cardiac event against its owndata collection (e.g. PPG data).

The situation of different medical or fitness tracking devices havingdifferent (i.e.: their own) internal clocks, timing systems, and delaytimes becomes increasingly problematic as further devices are added to alarger patient monitoring or operating system. For example, should asecond PPG device be used as well (for example, to simultaneously detectarterial pulse arrival and blood oxygenation on the fingers of bothhands), further inaccuracies are introduced if each PPG system has itsown internal clock without knowledge of how they relate to datacollection by the signaling device. As such, it becomes difficult tosimultaneously operate different medical and fitness tracking systemsfrom different manufacturers, since each of these different systems willhave their own internal clocks, and their own inherent signal processingdelays. What is instead desired is a synchronization system that iscapable of accurately operating with medical and fitness trackingdevices manufactured by many different device brands and suppliers.

Whether the signal delays are caused by “machine” delays (i.e.: signalprocessing delays caused by and within the system hardware itself), or“transmission” delays (i.e.: signal delays caused by the medium throughwhich the signal is carried) is immaterial from a calculation point ofview, so long as they are characterized and consistent. For example,signals travel faster between devices that are wired together, whereassignals appear to travel slower between wireless devices due to thesoftware processing needed at both ends. Moreover, signals also cantravel slower when passing through tissues than when passing wirelesslythrough the air. In the case where some of the medical or fitnessdevices are wired together, and some are in wireless communication, thevarious delays can become rather problematic. Since it is oftendesirable to operate various devices independently, but at the sametime, synchronizing their various timing operations and delays hasproven problematic (regardless of exactly how and why their signaldelays are caused). Thus, it is desirable to provide a system forsimultaneously synchronizing multiple devices to a cardiac cycle suchthat these multiple devices can be used on a patient all at the sametime, with all of the devices being accurately timed to one “true”cardiac cycle regardless of how their various signal delays are caused.

Yet another problem is that complex medical-type devices that accuratelymeasure the cardiac cycle can be quite expensive, whereas cheaperfitness-tracker-devices simply do not measure the cardiac cycle with thesame high level of accuracy and precision. As such, these cheaperfitness tracking devices cannot be used to calibrate other medical anddiagnostic devices such as PPGs. For example, to date it has not beenpossible to accurately measure a user's PWTT, or the pulse metrics thatassessment of PWTT can allow, using a simple fitness tracker. It wouldinstead be desirable to provide a system that measures the inherentprocessing delays, and by so doing synchronizes these cheaper fitnesstracking devices to the actual cardiac cycle. As a result, these cheaperfitness tracking devices could then be used to perform functions thattypically require much more expensive and/or bulky ECG systems (such asaccurately measuring PWTT). In short, it would be especially desirableto measure PWTT with an inexpensive fitness tracking device since thepulse metrics obtainable once PWTT is stable and reproducible and canprovide numerical assessment of health/fitness beyond what can beobtained from heart rate alone.

SUMMARY OF THE INVENTION

The present invention provides a system for synchronizing a targetdevice to a cardiac cycle, comprising: (a) a target device that performsan operation that is to be timed to a cardiac cycle; (b) a signalingdevice that emits a signal indicating the occurrence of a cardiaccontraction; and (c) a calibration device that determines the timing ofthe cardiac cycle. In operation, the calibration device receives thesignal from the signaling device and calculates a time offset betweenthe timing of the signal from the signaling device and the timing of thecardiac cycle as determined by the calibration device. The calibrationdevice then provides the time offset to the target device, therebyenabling synchronization of the target device to the cardiac cycle.

In preferred aspects, the time offset can be used either in targetdevice “sensing” scenarios where the time offset provided to the targetdevice comprises an adjustment of the times reported by the targetdevice sensing specific physiological features of the cardiac cycle. Inother preferred aspects, the time offset can be used in “performing anapplication” scenarios where the time offset provided to the targetdevice comprises an adjustment of the times at which the target deviceperforms actions based on specific physiological features of the cardiaccycle.

In preferred aspects, the time offset provided to the target device isused to perform an adjustment to the output of an internal clock in thetarget device. In various aspects, the signaling device may emit asignal having a fixed consistent time relationship to an actual heartcontraction. Alternatively, the signal may not be specific as to cardiaccycle phase. For example, the signal emitted by the signaling device mayidentify those points in time corresponding specifically to heartcontraction or the signal may correspond to other recurring points intime in the cardiac cycle that are not times of heart contraction.

In one preferred optional embodiment, the target device may be any oneof: a PPG system; a cardiac/blood property monitoring device; a drugdelivery device; a fluid sampling device; a fluid measuring device; arobotic surgery device; an imaging device; or a pacemaker. However,other possibilities are also contemplated, all keeping within the scopeof the present invention. The signaling device may be any one of: aheart rate measuring device, an ECG system, an imaging device, includingbut not limited to a fluoroscope, video-camera, MRI or CT machine, anacoustic device, including but not limited to a stethoscope, or aphysical sensing device capable of determining a heart contraction,including but not limited to a chest belt strap device. Again, otherpossibilities are also contemplated, all keeping within the scope of thepresent invention.

In further optional embodiments, any number of additional (same ordifferent types of) target devices can be added to the present system,with each one being accurately calibrated to the cardiac cycle using theabove described methods. In one preferred embodiment, the first andsecond target devices are both PPG systems configured to be positionedon different anatomical locations on a patient (for example, on oppositeleft and right limbs of a patient). In one exemplary configuration, thefirst target device is a PPG system, the signaling device is a simpleECG system (such as an ECG monitoring wrist watch or band), and thecalibration device is a different (i.e.: second) ECG system. It is to beunderstood that the signaling device could also be a simple heart ratemonitor such as a chest band monitor. Other possibilities are alsocontemplated, all keeping within the scope of the invention. In thesevarious exemplary arrangements, the calibration ECG system is incommunication with the target PPG system and the signaling system isalso in communication with the target PPG system. In preferred aspects,the time offset is the difference in time of the detection of a QRSsignal between each of the calibration ECG system and the signalingsystem.

In one exemplary system, the calibration ECG device is removed after thetime offset has been provided to the target device. Since thecalibration ECG system can be more expensive than a signaling ECGsystem, this approach has the advantage of cost savings since the sameexpensive ECG calibration system can then be used to synchronizemultiple, cheaper ECG (or non-ECG) signaling systems.

In various aspects where the signaling system is an ECG, the leads ofthe signaling ECG system may be disposed in opposite handlebars of anexercise machine or in opposite sides or ends of a hand-held device orhand-held device cover. Other possibilities are also contemplated, allkeeping within the scope of the present invention. For example, invarious aspects, the leads of the calibration device may be disposed ina single patch or a pair of patches worn on a person's skin. Inaddition, the leads of the calibration device can be disposed in anarticle of clothing or wearable garment including, but not limited to: aglove, a hat, a headband, a shirt/blouse, a pair of pants, a belt orstrap, ear buds or other headphones, a shoe, a sock, outerwear,underwear, a backpack, a handbag, a bag.

In yet another preferred embodiment, the first target device comprises aDoppler system, the signaling device comprises an MRI system, and thecalibration device comprises an ECG system. In this embodiment, thecalibration device is in communication with the first target device, andthe signaling device is also in communication with the first targetdevice. In these embodiments, the signaling device may be an MRI in Cinemode or an Echocardiogram system, and the first target device may be aPPG system.

In yet another exemplary embodiment, a system is provided forsynchronizing a target device to a cardiac cycle, comprising: (a) atarget device that performs an operation that is to be timed to acardiac cycle; and (b) a combined calibration-and-signaling device thatdetermines the timing of the cardiac cycle. In this embodiment, thecalibration-and-signaling device calculates a time offset between thetiming of the occurrence of the cardiac contraction and the timing ofthe cardiac cycle as determined by the calibration-and-signaling device,and the calibration-and-signaling device provides the time offset to thetarget device thereby enabling synchronization of the first targetdevice to the cardiac cycle. This arrangement has the cost savingadvantage of integrating the calibration and signaling devices into asingle device.

In preferred aspects, the signal that is synchronized to the cardiaccycle is a composite PPG signal that has been generated by comparing PPGsignal lengths to one another, wherein the PPG signal lengths aresegmented on the basis of repeating features in the cardiac cycle. Forexample, the composite PPG signal that is synchronized to the cardiaccycle may be generated by measuring the PPG signal over a plurality ofcardiac cycles, and then segmenting the signal into lengthscorresponding to cardiac cycle features and then comparing the signalsegments to one another. It is to be understood that a wide variety ofapproaches can be used for comparing these signal segments to oneanother to generate the representative composite signal, all keepingwithin the scope of the present invention. For example, signals may besegmented and then mathematically combined (e.g.: averaged, summed,combined through weighted averages, or combined through othermathematical approaches, etc.) over the full R-to-R length of thecardiac cycle signals each having a length from one R wave to the next Rwave. In other approaches, the signals may be segmented into lengthscorresponding to specific portions of the full cardiac cycle, and thenmathematically combined, or otherwise compared to one another. Inanother approach, the signal segments are compared to one another ormathematically combined after first being placed into categories or bins(corresponding to different pulse/cardiac cycle durations). In thisapproach, the signals in a category are compared against one another ormathematically combined to generate a composite waveform for thatcategory. In other approaches, segments may be compared against priorsegments to look for similarities. Systems may also be employed toreject signal outliers prior to comparing these segments to one another,all keeping within the scope of the present invention.

An advantage of using a composite PPG signal is that (as will be furtherexplained) motion artifacts, noise and other irregularities in ameasured PPG signal can be significantly reduced or even eliminated,thereby providing a signal that more accurately parallels actualphysiological functions. An advantage of using a composite PPG signal inthe present synchronization system is that by first having the PPG andECG systems' signals synchronized to one another, the generation of thecomposite PPG wave is very accurate, and thus provides an excellentrepresentation of cardiac functioning.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of the present system.

FIG. 2 is an illustration of the signal readings of the variouscomponents of a preferred embodiment of the present system.

FIG. 3A is an illustration of a preferred embodiment of the presentsystem using a removable calibration device (prior to removal of thecalibration device).

FIG. 3B is an illustration corresponding to FIG. 3B, but with thecalibration device removed.

FIG. 4A is an illustration of an exemplary calibration ECG systempositioned on a patient's chest, with an exemplary signaling ECG systemand target PPG system disposed in a band around the patient's arm.

FIG. 4B is a sectional view through the patient corresponding to FIG.4A.

FIG. 5A is a top perspective view of an exemplary signaling and targetdevice disposed in an adhesive chest patch.

FIG. 5B is a bottom perspective view of the exemplary signaling andtargeting device of FIG. 5A.

FIG. 5C illustrates exemplary signaling and targeting devices disposedin a chest strap worn by the patient.

FIG. 6A is an exemplary handheld signaling and target device positionedon a patient's chest.

FIG. 6B is a sectional view through the patient corresponding to FIG.6A.

FIG. 7A is a top perspective view of an exemplary signaling andtargeting device that is held in a patient's hands.

FIG. 7B is a bottom perspective view of the signaling device of FIG. 7A.

FIG. 8A illustrates ECG and PPG signals measured over a plurality ofcardiac cycles.

FIG. 8B illustrates the generation of a PPG composite signal fromaveraged PPG signal segments corresponding to successive cardiac cycles.

FIG. 9 is a first side-by-side comparison of ECG and PPG signals showingsteps in an alternate method of generating a PPG composite wave.

FIG. 10 is a second side-by-side comparison of ECG and PPG signalsshowing steps in an alternate method of generating a PPG composite wave.

DETAILED DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of the present system 10 forsynchronizing one or more target devices T1, T2 . . . Tn to a cardiaccycle. System 10 comprises: (a) at least one target device T1 (T2 . . .to Tn) that performs an operation that is to be timed to a cardiaccycle; (b) a signaling device S that emits a signal indicating theoccurrence of a cardiac contraction; and (c) a calibration device C thatdetermines the timing of the cardiac cycle. As will be explained hereinwith reference to FIG. 2, the calibration device C receives a signalfrom signaling device S and then calibration device C calculates a timeoffset TO between the timing of the heart contraction as determined bythe signaling device S and the timing of the heart contraction in thecardiac cycle as determined by the calibration device C. Next, as willalso be fully explained, the calibration device C provides the timeoffset TO to target device T1 thereby enabling synchronization of targetdevice T1 to the cardiac cycle.

In optional preferred embodiments of the present system, the firsttarget device T1 (and various additional target devices T2 to Tn) mayeach be one of the following systems or devices: a PPG(photoplethysmography) system; any cardiac/blood property monitoringdevice; a drug delivery device; a fluid sampling device; a fluidmeasuring device; a robotic surgery device; an imaging device; or apacemaker. It is to be understood, however, that the present targetdevice T1 to Tn are not limited to only to these specific devices. It isalso to be understood that the present system encompasses embodimentswith only one target device T1, and embodiments with any plurality oftarget devices T1 to Tn.

In optional preferred embodiments of the present system, the signalingdevice S may be one of the following systems and devices: a heart ratemeasuring device, an ECG system, an imaging device, including but notlimited to a fluoroscope, video-camera, MRI or CT machine, an acousticdevice, including but not limited to a stethoscope, or a physicalsensing device capable of determining a heart contraction, including butnot limited to a chest belt strap device.

Optionally, a plurality of target devices T1 to Tn each perform anoperation that is to be accurately timed to the cardiac cycle, and thecalibration device C provides the time offset TO to each of these targetdevices, thereby enabling synchronization of each of the plurality oftarget devices to the cardiac cycle.

In one preferred embodiment of the present system (further explained inFIG. 2 and FIGS. 3A and 3B), the signaling device S is a first ECGsystem, the calibration device is a second ECG system and the targetdevice is a PPG system. (Preferably, the signaling device S can be asimple, inexpensive ECG system such as a system in a wrist watch orband, or in a chest band; whereas the calibration ECG system C can be amore expensive and more accurate ECG system).

In another preferred embodiment of the present system, the signalingdevice S is an MRI system, the calibration device is an ECG system andthe target device is a Doppler system. Optionally, the signaling deviceS may instead be an MRI in Cine mode or an Echocardiogram system, andthe target device may instead be a PPG system.

In each of these various embodiments above, the calibration device C isin communication with the target device T1, and the signaling device Sis also in communication with target device T1.

In optional embodiments of the present system, the calibration andsignaling devices are combined into an integrated device that performsboth functions. As such, a system for synchronizing a first targetdevice to a cardiac cycle is provided, comprising: (a) a targetdevice(s) that performs an operation that is timed to a cardiac cycle;and (b) a calibration-and-signaling device that determines the timing ofthe cardiac cycle. In this embodiment, the calibration-and-signalingdevice calculates a time offset between the timing of the occurrence ofthe cardiac contraction and the timing of the cardiac cycle asdetermined by the calibration-and-signaling device, and thecalibration-and-signaling device provides the time offset to the firsttarget device thereby enabling synchronization of the first targetdevice to the cardiac cycle.

FIG. 2 is an illustration of the signal readings of the variouscomponents of one preferred embodiment of the present system, asprovided by the various components of an exemplary embodiment of thepresent system (as further illustrated in FIGS. 3A and 3B), as follows.

The signal emitted by signaling device S is a repeating waveformgenerally corresponding to the user's cardiac cycle, showing the timesat which the heart's QRS wave is detected. Similarly, the signalsdetected by calibration device C is also a repeating waveform generallycorresponding to the user's cardiac cycle, also showing the times atwhich the heart's QRS wave is detected. As can be seen, the signalingand calibration devices S and C do not detect the heart's QRS wave atexactly the same times. This is due to the fact that the signalingdevice S may be a cheaper, simpler device having an inherent signal timedelay (as compared to the more sophisticated calibration device C). Inaddition, the delay in the signal from signaling device S results bothfrom the combination of the delay in the circuit itself (i.e.: the timespent for signaling device S to read and transmit its signal) and thedelay in the signal traveling across the body (for example, the signaltraveling from a different body location from that of calibration systemC).

As can be seen, the time offset TO is the difference in time of thedetection of a QRS signal between each of the calibration and signalingsystems C and S. In accordance with the present invention, thecalibration system C senses the cardiac cycle, and knowing its own delayproperties it determines the time offset TO that is then provided totarget device T1 so that the target device T1 can synchronize to thecardiac cycle.

In one preferred method, the time offset TO provided to the first targetdevice T1 comprises an adjustment to be made to the internal clockoutput in target device T1. As such, the time offset TO provided to thefirst target device T1 may either comprise an adjustment of the timesreported by the first target device when sensing specific physiologicalfeatures of the cardiac cycle, or the times of performing actions basedon specific physiological features of the cardiac cycle.

In the preferred exemplary aspect illustrated in FIGS. 3A and 3B, thetime offset TO provided by calibration system C will be used to permittarget device T1 to accurately measure a patient or user's PWTT (so asto generate various pulse metrics). It is to be understood, however,that many other applications of the present system are also contemplatedwithin the scope of the present invention.

In various aspects of the present system, the signaling device S emits asignal that either: has a fixed consistent time relationship to anactual heart contraction, or is not specific as to cardiac cycle phase.For example, the signaling device may emit a simple “beep” only atpoints in time when it senses a heart contraction, or it may emit acontinuous signal that corresponds to other known points in a cardiaccycle that are not times of heart contraction. In the illustration ofFIG. 2, the signaling device emits a continuous ECG signal.

Typically, for the signaling device S, it is expected that the signalprocessing delays (i.e.: delays within the circuitry itself) will be themajor delay factor and that delays caused by individual patientphysiology (i.e.: the speed of travel of electrical signals through thepatient's body) will be small. The speed at which signals travel throughthe patient's body can vary over time as the patient's health changes.Also, different types of signaling devices S will have different delays.All of these delays will be consistent for one patient with one set ofdevices at one time. The present system can effectively deal with allthese irregularities since it relies upon a more accurate calibrationECG system C to determine the exact timing of the cardiac cycle.

In the embodiments illustrated in FIGS. 3A and 3B, the first targetdevice T1 comprises a first PPG system, the second target device T2comprises a second PPG system, the signaling device S comprises a first(simple, less accurate) ECG system, and the calibration C devicecomprises a second (more accurate) ECG system. The calibration device Cis in communication with the target devices T1 and T2, and the signalingdevice S is also in communication with the target devices T1 and T2.

In the illustrated embodiment, the first and second target devices T1,T2 are both PPG systems configured to be positioned on differentanatomical locations on a patient, for example, the opposite laterallimbs of a patient (e.g.: fingers on the patient's left and righthands).

The objective of the system illustrated in FIGS. 3A and 3B is to easilycalculate the patient's simultaneous PWTT to each of the patient'sopposite limbs. (It is to be understood that target device T2 can beremoved from FIGS. 3A and 3B so that the system instead functions onlyto calculate the PWTT to one limb at a time).

A user can keep track of their personal fitness by monitoring the pulsemetrics obtainable once a stable/reproducible PWTT is established forany given scenario. Such pulse metrics (shape/slope/peaks/rolloff, etc.)provide insight into the cardiovascular status of the individual, suchas whether peripheral arterial resistance is high or low.

In the illustrated embodiment of FIGS. 2, 3A and 3B, PWTT is determinedby measuring the time difference between the onset of the heartcontraction (i.e.: the accurate time detection of the QRS signal asmeasured by the calibration ECG system C) and the time at which the peakarterial pulse reaches a desired location on the patient's body (i.e.:the accurate time detection of the maximum and minimum of the signalreading taken by a PPG device T1 at a patient's finger tips). A PPG(photoplethysmography) system measures changes in the light reflectedfrom or transmitted through the illuminated skin. The blood pulse wavedistends the arterioles as it passes through them. Therefore, thearrival time of each pulse in the cardiac cycle can be read as a maximum(the onset of the arterial pulse) and a minimum (at the peak of thepulse) in the signal from the PPG's light sensor.

A major problem with using existing ECG and PPG systems together is thatthey typically each have their own dedicated internal clocks whichmeasure time separately. As such, synchronizing ECG and PPG time signalshas proven to be especially problematic because of the effect of verysmall (microsecond to millisecond) differences in clock timing. Theseproblems occur even with signal time differences even being a fewmicroseconds or milliseconds apart. In addition, problems also occurwith simple ECG signaling systems due to the high noise to signal ratioand potential for outside interference. Measuring a patient's ECG with asimple fitness tracker signaling device is also problematic due tointermittent connections inherent in poor skin connection. Motion of thepatient also degrades the accuracy when taking an ECG reading with asimple device. Moreover, the most accurate ECG readings are taken whenthe ECG leads are positioned far apart on the patient. As such, the mostaccurate ECG measurement approaches tend to be the ones that are mostintrusive, or require the patient to remain motionless in a hospital ordoctor's office. It would instead be desirable to provide an accurate,synchronized ECG system that can be used while moving or exercising. Thepresent solution addresses these concerns and enables a person tosimply, cheaply (and accurately) measure their own arterial pulsemetrics in the convenience of their own home or place of exercise.

Prior art solutions instead often relied on a (3^(rd)) master clock tosend time signals to each of the internal clocks of the ECG and PPGmonitoring systems. Objectives of the present system are to achieve timesynchronization: (a) without relying on a 3rd master clock, (b) withoutrelying on a 2nd separate clock timing in one of the ECG or PPG systems,and (c) without having to determine which of two clocks is “morecorrect”, and then make adjustments or apply some form of averages tothese multiple clocks.

Another objective of the present system is the removal of the wiredconnection between the ECG and PPG monitoring systems. As such, thepresent system can conveniently be used when exercising.

Another objective of the present system is to employ the best placementfor each of the ECG and PPG sensors on the body. With the presentsystem, optimal placement of each of the ECG and PPG sensors on the bodycan be achieved, with the present system providing the requiredcalibration.

Should two PPG devices T1, T2 be used as in FIGS. 3A and 3B, (i.e.: withone located on each of the patient's opposite hands or toes), then isthen possible to determine if the blood wave from the heart reaches thetwo hands (or feet) at the same time. A detected time difference in thePWTT or pulse metrics for the arterial pulse seen in opposite handscould (for an adult) indicate a diabetic problem, or (for a newborn)indicate problems with a delayed sealing of the ductus arteriosis thatoccurs within 2-4 days after birth. Performing such a diagnosticprocedure would inherently require that the two PPG devices be measuringthe cardiac cycle at exactly the same time. In short, the two PPGdevices would both need to be synchronized to the same cardiac cycletiming. As explained herein, the present system can be used tosynchronize multiple devices to the same cardiac cycle.

Returning to FIG. 2, the PWTT TIME is the time from the calibrationsystem C detecting the QRS wave to the time the target PPG device T1 (orT2) detects maximum arterial blood volume. This is represented on FIG. 2as the signal from T1. (The signal from tracking device T2 is omittedfrom FIG. 2 for clarity).

As can be seen, the (cheaper, simpler) signaling device S will detectthe QRS wave at a slightly delayed time as compared to the (moreexpensive and more accurate) calibration device C. Therefore, byadjusting targeting device T1's internal clock back by the time offsetTO, a correct PWTT TIME can be determined. Stated another way, thedifference in time between the signals from devices S and C will beprovided to target device T1 enabling it to synchronize signaling to thecardiac cycle. Stated yet another way, after system calibration, inessence the signaling ECG system S shares the same internal clock of thecalibration ECG system C.

An advantage of the present system is that it is only necessary todetermine the timing of the QRS wave with each one of the S and Cdevices. Thus, it is only necessary to determine when the maximum PPG(and ECG) signals occurs. Importantly, it is not necessary to exactlydetermine the exact level of these signals. Therefore, an advantage ofthe present system is that different ECG and PPG systems can be used(with the present system compensating for differences i.e.: systemcalculation delays) between different manufacturers.

As shown in FIG. 3B, the calibration ECG device C can be removed afterthe time offset TO has been provided to the first PPG target device T1(and optionally to a second target device T2). As a result, a singleexpensive calibration system C can be used to calibrate multiple targetdevices T1, T2, etc. This allows cheaper, fitness-monitoring watches andbands to be synchronized to a patient's cardiac cycle such that they canbe used to accurately measure a fitness enthusiast's pulse metrics(after calculating PWTT). Periodic recalibration of the target device(s)can be done to the PPG device(s) T1 (and T2).

An important advantage of calibrating a fitness-monitoring watch or band(i.e.: signaling device S) to a patient's cardiac cycle is that thesignaling device S can be a small, lightweight, inconspicuous andcomfortable device that can be worn while exercising. As such, a moreexpensive, bulky, yet highly accurate ECG system (i.e.: calibrationdevice C) need not be required during exercise or continued use.

To date, accurate PWTT measurements require an expensive, highlyaccurate ECG system that accurately detects the exact moment of theheart's QRS signal. This currently is done in a research setting, or aspart of a clinical trial. The present calibration system avoids thisproblem. Using the present system and techniques, it is possible toaccurately determine a patient's PWTT (since the inexpensive, lessaccurate ECG signaling system S is first accurately synchronized to thecardiac cycle. As a result, simple, cheaper ECG devices (such as thosein various fitness watches and trackers) can be used to accuratelydetermine PWTT. As such, the more expensive and accurate ECG calibrationdevice C need only be used only for initial system calibration.

In optional embodiments, the leads of the signaling ECG system S can bedisposed in opposite handlebars of an exercise machine. The leads of thesignaling or calibration ECG devices can optionally be disposed inopposite sides or ends of a hand-held device (such as a smartphone orstethoscope).

FIGS. 4A and 4B illustrate an exemplary ECG calibration system for usewith a signaling PPG system and target ECG system. In this example, anexisting telemetry system 90 functions as the calibration system (i.e.:telemetry system 90 corresponds to system C in FIG. 3A). An arm strap 80houses both the target and signaling systems (corresponding toillustrated T and S systems in FIGS. 3A and 3B). Arm strap system 80wraps around the patient's arm (or leg) and includes a right electrode54 and a PPG sensor 60. The left electrode 52 extends across thepatient's chest to measure electrical signals on the left side of thepatient's heart. In the embodiment shown in FIG. 4A, the present systemsimply piggy-back connects left chest electrode 52 on an existingtelemetry system electrode 91 from telemetry system 90. Specifically, astackable rivet-type electrode snap may be provided such that armelectrode 52 can quickly and easily be attached to the opposite chestelectrode 91. In various embodiments, the electrodes may be wet or dryelectrodes. An advantage of using wet electrodes is that they tend toprovide a stronger, more stable signal. It is to be understood that thepresent system does not require telemetry system 90 to be used on thepatient at the same time as the present system. As such, telemetrysystem 90 (and its associated electrode 91) can be removed from thepatient after the calibration has been performed (as illustrated in FIG.3B where C has been removed).

FIGS. 5A and 5B illustrate an exemplary adhesive patch system 150housing both signaling and target devices (corresponding to systems Sand T in FIGS. 3A and 3B), as follows. Integrated patch system 150 canbe used to measure a person's PWTT/pulse waveform. Patch 150 maypreferably comprise a left electrode 152 and a right electrode 154 formeasuring ECG readings across the patient's heart. A PPG sensor 160 isalso provided. Electrode 154 may also optionally be a “snap” electrodethat simply piggy-back connects left chest electrode 152 on an existingtelemetry system electrode (i.e.: electrode 91 from telemetry system 90in FIG. 4A).

FIG. 5C illustrates a similar chest strap device 50 housing bothsignaling and target devices (again corresponding to systems S and T inFIGS. 3A and 3B), as follows. Chest belt or strap mounted device 50 canbe used to measure a person's PWTT/pulse waveform. Strap device 50 maypreferably comprise a strap body 51 with a left electrode 52 and a rightelectrode 54 for measuring ECG readings across the patient's heart. ThePPG sensor 60 is disposed on the patient-facing side of strap body 51.FIG. 5C illustrates the positioning of the signaling device along thelines of the adhesive patch system of FIGS. 5A and 5B, but when thedevice is instead positioned within a chest strap worn by the patient.

FIGS. 6A and 6B illustrate yet another exemplary device housing bothsignaling and target devices (corresponding to systems S and T in FIGS.3A and 3B), as follows. Device 10 is a chest or side mounted device formeasuring pulse waveforms. Device 10 comprises a housing (that ispreferably shaped to be hand-held, as shown), having a first (leftchest) electrode 12 and a second (right chest) electrode 14 thereon. AnECG system (corresponding to signaling system S in FIGS. 3A and 3B) isdisposed within the housing of device 10 and is in electricalcommunication with electrodes 12 and 14. When device 10 is positioned ona patient's chest as shown, electrodes 12 and 14 are thus positionedacross the patient's heart to take ECG readings on the patient. At leastone (but preferably a plurality) of PPG sensor(s) 20 (corresponding totarget system T in FIGS. 3A and 3B) are also disposed on the housing ofdevice 10. Logic for measuring the PPG signal from sensor 20 is disposedwithin the housing of device 10. Also disposed within the housing ofdevice 10 are control and communication systems, and preferably abattery or other source of power. An optional right electrode lead canbe plugged into the housing of device 10 such that the patient's ECG canbe measured across the patient's torso (when the patient is in a proneposition).

FIGS. 7A and 7B illustrate an exemplary handheld signaling and targetingdevice that is held in a patient's hands. Device 200 has a pair ofelectrode handles 202 onto which a user grasps. The user simply holdselectrode handles 202 and then uses their thumb to push start button203. The user then immediately moves their thumb or finger to bepositioned against PPG sensor 204. Holding onto electrode handles 202completes a circuit across the heart allowing the ECG system in device200 to measure ECG waveforms. The PPG sensor 204 allows the PPG systemin device 200 to measure PPG waveforms. As such, the ECG system indevice 200 corresponds to the signaling system S and the PPG system indevice 200 corresponds to the target system T in FIGS. 3A and 3B. FIG.7B shows a bottom screen that optionally displays a Pulse Wave TransitTime.

As stated above, the present calibration system preferably uses a“composite” PPG signal that is synchronized to the cardiac cycle. Aswill now be explained, the composite PPG signal is preferably generatedby comparing various lengths of PPG signal segments to one another, andthese signal lengths are preferably segmented on the basis of repeatingfeatures in the cardiac cycle. As will also be explained, the generationof such a composite signal PPG waveform mitigates the current problemsof signal noise and motion artifacts when measuring a patient's PPGsignals, as follows.

When wearable sensors are used during exercise or other motion, theinterference from internal and external sources such as from bodymovement, muscular contractions, wire friction, external RFinterference, as well as noise from the sensor itself can make the rawsensor output appear unusable. Noise and signal errors are especiallycommon when dealing with PPG sensors on ambulatory patients. Such errorsand noise become very pronounced when a patient is moving. As such,accurate PPG monitoring has proven to be difficult to perform on peoplethat are exercising or otherwise moving around.

Existing systems tend to use high and/or low pass filters in an attemptto clean up the data signal. Unfortunately, applying high and/or lowpass filters to PPG data can, and often does, remove or change importantunderlying signal information, such as peaks and valleys in the timedomain. Moreover, attempts at mathematically averaging the PPG datasignals utilizing only its own waveform characteristics (onset, maximum,duration) have been similarly imperfect in removing spurious readingswhile providing consistent accurate results. As a result, the existingsystems for determining pulse metrics required invasive procedures (suchas right or left heart catheterization with pressure monitors) tomeasure cardiac pressures and pulsations. Such invasive tests aretherefore only reserved for situations wherein the benefits ofintervention are deemed to exceed the very significant risks of thetests themselves. In contrast, the present system instead provides is asystem for quickly producing reliable PPG signals such that pulsemetrics can be determined accurately (and preferably without having torestrain the motion of the patient, while also not using high or lowpass filtering which can remove important data from the signal). As willbe shown, this preferred system provides data from patients in motionthat is consistently usable for analysis by removing large amounts ofnoise from motion and other artifacts.

In various aspects, the present invention provides systems for removingmotion and ambient variability from PPG sensor data to improve discoveryof the underlying unfiltered PPG waveform. As such, the present system'snovel computerized logic system includes various optional circuitry andlogic systems that remove or compensate for the effects of noise in thePPG signal, as follows.

As seen in FIG. 8A, an ECG signal 200 is measured over a plurality ofcardiac cycles. Specifically, the onset of the heart's R-wave of the QRScomplex occurs repeatedly at points 202. The PPG system measures the PPGsignal 300's strength over the same time period (i.e.: over a pluralityof cardiac cycles). In accordance with the present system, the PPGsignal is then segmented in lengths corresponding to the length of thecardiac cycle. For example, a first segment 300 ₁ will be measured overthe first cardiac cycle (i.e. between times to and t₁), a second segment300 ₂ will be measured over the second cardiac cycle (i.e. between timest₁ and t₂), and a third segment 300 ₃ will be measured over the thirdcardiac cycle (i.e. between times t₂ and t₃). Next, as seen in FIG. 8B,segments 300 ₁, 300 ₂ and 300 ₃ can be averaged to produce arepresentative or “composite” signal segment 300C. It is to beunderstood that the use of three segments in FIGS. 8A and 8B is merelyexemplary. For example, a greater number of PPG signal segments 300 nmay be used to generate the representative or composite signal segment300C.

As a result, the present system advantageously removes signal errors bytaking a long PPG signal reading 300 (i.e.: lasting greater than severalcardiac cycles), and then dividing the PPG signal into segmentscorresponding to the timing of the cardiac cycles. Preferably, thepresent PPG signal reading 300 is parsed or segmented based upon thetiming of the cardiac QRS rhythm. Importantly, once the full waveform300C has been generated and plotted in accordance with the presentsystem, analysis of the exact shape of the waveform (or waveformsgenerated or extracted from this waveform) can be used to calculatevarious pulse wave metrics or observe other cardiac system features.

In other preferred aspects, generation of the composite PPG signal isperformed by selecting PPG signal waveforms of similar R-to-R intervalsof the pulse/cardiac cycle prior to the pulse/cardiac cycle in question.In various aspects, characteristics such as peak height, peak width,slope and duration can all contribute to a calculation that isaccurately representative of that particular wave form.

FIG. 9 is a first side-by-side comparison of ECG and PPG signals showingsteps in an alternate method of generating a PPG composite wave.Specifically, an ECG signal 400 is taken over five pulses/cardiac cycles(labelled pulses A, B, C, D and E). A PPG signal 500 is also taken overthe same five pulses/ cardiac cycles (A, B, C, D and E). As can be seen,each of the five pulse lengths are not of exactly equal duration (whichis to be expected as an individual's heart rate will vary over time). Inaccordance with this aspect of the present invention, the PPG signalwill first be segmented and put into categories or “bins” representingsegments of approximately equal lengths. Stated another way, all of the“short” segments can be grouped, categorized and analyzed together, allof the “intermediate length” segments can be categorized and analyzedtogether, and all of the “long duration” segments can be categorized andanalyzed together. As such, separate composite waves can be generatedfor each of the short, intermediate and long categories of waveformsegments. This is particularly useful in that some cardiac conditions orfeatures may best be analyzed for an intermediate length pulse, whereasother cardiac conditions or features may best be analyzed for a short orlong duration pulses. In fact, further insights may be gained bycomparing composite PPG waveform segments from one category withanother. For example, it is expected that certain cardiac conditions maybe detected when a certain feature is seen in their intermediate lengthcategory while another feature is seen in their short or long compositewaveform category. A wide variety of possibilities exist. It istherefore to be understood that a large variety of possible combinationsexist, and the present invention is not limited to looking only at onecategory of waveform length or another. Instead, it is possible tocompare composite waveforms from different categories to one another.Moreover, it is to be understood that the present invention is notlimited to only three categories (i.e.: short duration, intermediateduration and long duration categories). For example, additional or fewercategories may be used (e.g.: very short, short, short-intermediate,standard-intermediate, long-intermediate, long and very long). It is tobe understood that analysis may also be performed by only analyzing onlyone category's composite signal, or by also analyzing more than onecategory's composite signal.

In one exemplary approach seen in FIGS. 9 and 10, the pulses are sortedinto categories based on the length of the previously measured pulse(and not the length of the current pulse being measured). The advantageof this novel approach is that it categorizes waveforms on the basis ofsimilar ventricular fillings. Specifically, the filling stage of theheart in one cardiac cycle will correspond to the squeezing or emptyingstage of the heart in the next cardiac cycle. Stated another way, thepre-contraction ventricular filling state will depend upon the timeavailable to fill after the last contraction. Ventricular function willtherefore vary beat to beat depending upon the variability of the pulselength. As such, R-to-R pulses are preferably compared in pairs, withthe second pulse being categorized on the basis of the length of thefirst pulse, as follows.

In FIG. 9, Pulses B and E are categorized on the basis of theirimmediately previous pulses (i.e.: Pulse A and Pulse D). Since Pulses Aand D were intermediate duration pulses; Pulses B and E are thereforeplaced together in the intermediate length category (even though PulsesB and E have considerably different lengths).

FIG. 10 shows a longer series of pulses A to I. The prior R-to-Rcategorization (in which two successive pulses are analyzed together)proceeds as follows. Pulses B and C are analyzed together as a first “2beat complex”. C is placed into a category corresponding to the lengthof B. Next, pulses C and D are analyzed together as a second “2 beatcomplex”. D is placed into a category corresponding to the length of C.Next, pulses D and E are analyzed together and E is placed into acategory corresponding to the length of D. Next, pulses E and F areanalyzed together and F is placed into a category corresponding to thelength of E, etc.

Moreover, it is to be understood that the categorizations of waveformsegments illustrated in FIGS. 9 and 10 can also be re-categorized andthen re-analyzed over a longer period of time. At that time, the variouscategories into which the segments are placed can also be changed toperform additional analysis. For example, it may make sense to recordECG signal 400 and PPG signal 500 over several hundred cardiac cycles.Once all this data has been recorded and the waveforms segmented intotheir R-to-R segments (or otherwise segmented based on repeatingidentifiable cardiac features), then the present system can go back andplace the segments into different categories. For example, thesesegments can be placed into three categories (short, intermediate andlong), or more categories (e.g.: very short, short, short-intermediate,standard-intermediate, long-intermediate, long and very long). It is totherefore be understood that an advantage of the present system is thatdifferent forms of analysis based on placing the same signal segmentsinto different categories and then analyzing these segments at differenttimes can yield different useful results. As can also be appreciated,not only does the present system therefore provide an excellent systemof categorizing and analyzing waveforms, but it can also readilydetermine and report on a patient's heart rate variability.

It is to be understood that the present invention encompasses all formsof composite wave generation, and all forms of segmenting pulsewaveforms to group the segments into self-similar groups, categories orbins of different time durations. For various cardiac conditions,analysis of one category (e.g.: the intermediate duration segments) mayyield the best diagnostic results. For other cardiac conditions,analysis of another category (e.g.: the long duration segments) mayyield the best diagnostic results. It all depends upon which medicalcondition the present system is diagnosing at the time. The advantage ofthe present system is that it provides a novel platform to categorizethe waveform segments based on their relationships to the one another ingeneral, and to the segment that immediately precedes it in particular.

What is claimed is:
 1. A system for synchronizing a first target deviceto a cardiac cycle, comprising: (a) a first target device that performsan operation that is timed to a cardiac cycle; (b) a signaling devicethat emits a signal indicating the occurrence of a cardiac contraction;and (c) a calibration device that determines the timing of the cardiaccycle, wherein the calibration device receives the signal from thesignaling device and calculates a time offset between the timing of thesignal from the signaling device and the timing of the cardiac cycle asdetermined by the calibration device, and wherein the calibration deviceprovides the time offset to the first target device thereby enablingsynchronization of the first target device to the cardiac cycle.
 2. Thesystem of claim 1, wherein the time offset provided to the first targetdevice comprises an adjustment to an internal clock in the targetdevice.
 3. The system of claim 1, wherein the signaling device emits asignal having a fixed consistent time relationship to an actual heartcontraction.
 4. The system of claim 3, wherein the signal emitted by thesignaling device identifies points in time in the cardiac cycle that arenot times of heart contraction.
 5. The system of claim 1, wherein thefirst target device is one of: a PPG system; a cardiac/blood propertymonitoring device; a drug delivery device; a fluid sampling device; afluid measuring device; a robotic surgery device; an imaging device; ora pacemaker.
 6. The system of claim 1, wherein the signaling device is:a heart rate measuring device, an ECG system, an imaging device,including but not limited to a fluoroscope, video-camera, MRI or CTmachine, an acoustic device, including but not limited to a stethoscope,or a physical sensing device capable of determining a heart contraction,including but not limited to a chest belt strap device.
 7. The system ofclaim 1, further comprising: (d) a second target device that performs anoperation that is timed to the cardiac cycle, wherein the calibrationdevice provides the time offset to the second target device therebyenabling synchronization of the second target device to the cardiaccycle.
 8. The system of claim 7, wherein the first and second targetdevices are both PPG systems configured to be positioned on differentanatomical locations on a patient.
 9. The system of claim 1, wherein:the first target device comprises a PPG system, the signaling devicecomprises an ECG system, and the calibration device comprises an ECGsystem, and wherein the calibration device is in communication with thefirst target device, and the signaling device is in communication withthe first target device.
 10. The system of claim 9, wherein thesignaling ECG system shares the internal clock of the calibration ECGsystem.
 11. The system of claim 9, wherein the time offset is thedifference in time of the detection of a QRS signal between each of thecalibration and signaling ECG systems.
 12. The system of claim 1,wherein the leads of the signaling or calibration device are disposed inopposite sides or ends of a hand-held device or hand-held device cover.13. The system of claim 1, wherein the leads of the calibration deviceare disposed in a patch worn on a person's skin.
 14. The system of claim1, wherein the calibration device is removed after the time offset hasbeen provided to the first target device.
 15. The system of claim 1,wherein the signal emitted by the first target device is a composite PPGsignal.
 16. The system of claim 15, wherein the composite PPG signal isgenerated by comparing segments of a PPG signal taken over a pluralityof cardiac cycles.
 17. The system of claim 16, wherein comparing thesegments of the PPG signal comprises comparing segment lengths of thatsegment or prior segment to one another and then sorting segments ofsimilar length into categories and then generating composite signalsegments for each of the categories.
 18. A system for synchronizing afirst target device to a cardiac cycle, comprising: (a) a first targetdevice that performs an operation that is timed to a cardiac cycle; and(b) a calibration-and-signaling device that determines the timing of thecardiac cycle, wherein the calibration-and-signaling device calculates atime offset between the timing of the occurrence of the cardiaccontraction and the timing of the cardiac cycle as determined by thecalibration-and-signaling device, and wherein thecalibration-and-signaling device provides the time offset to the firsttarget device thereby enabling synchronization of the first targetdevice to the cardiac cycle.
 19. The system of claim 18, wherein thesignal emitted by the first target device is a composite PPG signal. 20.The system of claim 19, wherein the composite PPG signal is generated bycomparing segments of a PPG signal taken over a plurality of cardiaccycles.